A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia
Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure i...
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| Veröffentlicht in: | Leukemia 2015-07, Vol.29 (7), p.1478-1484 |
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| creator | Russell, N H Kjeldsen, L Craddock, C Pagliuca, A Yin, J A Clark, R E Howman, A Hills, R K Burnett, A K |
| description | Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35–44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50–0.85),
P
=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01–2.21),
P
=0.04) due to lower NRM (34 vs 14%,
P
=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57–0.97),
P
=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35–44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (
P
=0.3). |
| doi_str_mv | 10.1038/leu.2014.319 |
| format | Article |
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P
=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01–2.21),
P
=0.04) due to lower NRM (34 vs 14%,
P
=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57–0.97),
P
=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35–44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (
P
=0.3).</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2014.319</identifier><identifier>PMID: 25376374</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308/575 ; Acute myelocytic leukemia ; Acute myeloid leukemia ; Adult ; Allografts ; Analysis ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cancer Research ; Care and treatment ; Chemotherapy ; Combined Modality Therapy ; Conditioning ; Critical Care Medicine ; Cytogenetics ; Female ; Follow-Up Studies ; Graft vs Host Disease - mortality ; Graft vs Host Disease - prevention & control ; Health aspects ; Health risk assessment ; Health risks ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Intensive ; Internal Medicine ; Leukemia ; Leukemia, Myeloid, Acute - mortality ; Leukemia, Myeloid, Acute - pathology ; Leukemia, Myeloid, Acute - therapy ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mortality ; Mud ; Neoplasm Staging ; Oncology ; original-article ; Prognosis ; Remission ; Risk factors ; Siblings ; Stem cell transplantation ; Stem cells ; Survival ; Survival Rate ; Transplantation ; Transplantation Conditioning ; Transplantation, Homologous ; Transplants ; Transplants & implants ; United Kingdom ; Unrelated Donors</subject><ispartof>Leukemia, 2015-07, Vol.29 (7), p.1478-1484</ispartof><rights>Macmillan Publishers Limited 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2015</rights><rights>Macmillan Publishers Limited 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-90941c6b8faa11b181c5caac730af0c2726a623c5a2b4d10f43cc4256329aca13</citedby><cites>FETCH-LOGICAL-c624t-90941c6b8faa11b181c5caac730af0c2726a623c5a2b4d10f43cc4256329aca13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25376374$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Russell, N H</creatorcontrib><creatorcontrib>Kjeldsen, L</creatorcontrib><creatorcontrib>Craddock, C</creatorcontrib><creatorcontrib>Pagliuca, A</creatorcontrib><creatorcontrib>Yin, J A</creatorcontrib><creatorcontrib>Clark, R E</creatorcontrib><creatorcontrib>Howman, A</creatorcontrib><creatorcontrib>Hills, R K</creatorcontrib><creatorcontrib>Burnett, A K</creatorcontrib><creatorcontrib>UK NCRI Adult AML Working Party</creatorcontrib><creatorcontrib>Written on behalf of the UK NCRI Adult AML Working Party</creatorcontrib><title>A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35–44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50–0.85),
P
=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01–2.21),
P
=0.04) due to lower NRM (34 vs 14%,
P
=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57–0.97),
P
=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35–44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (
P
=0.3).</description><subject>692/308/575</subject><subject>Acute myelocytic leukemia</subject><subject>Acute myeloid leukemia</subject><subject>Adult</subject><subject>Allografts</subject><subject>Analysis</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Combined Modality Therapy</subject><subject>Conditioning</subject><subject>Critical Care Medicine</subject><subject>Cytogenetics</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Graft vs Host Disease - mortality</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Mud</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>original-article</subject><subject>Prognosis</subject><subject>Remission</subject><subject>Risk factors</subject><subject>Siblings</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Transplantation</subject><subject>Transplantation Conditioning</subject><subject>Transplantation, Homologous</subject><subject>Transplants</subject><subject>Transplants & implants</subject><subject>United Kingdom</subject><subject>Unrelated 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comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia</title><author>Russell, N H ; Kjeldsen, L ; Craddock, C ; Pagliuca, A ; Yin, J A ; Clark, R E ; Howman, A ; Hills, R K ; Burnett, A K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-90941c6b8faa11b181c5caac730af0c2726a623c5a2b4d10f43cc4256329aca13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>692/308/575</topic><topic>Acute myelocytic leukemia</topic><topic>Acute myeloid leukemia</topic><topic>Adult</topic><topic>Allografts</topic><topic>Analysis</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Chemotherapy</topic><topic>Combined Modality Therapy</topic><topic>Conditioning</topic><topic>Critical Care Medicine</topic><topic>Cytogenetics</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Graft vs Host Disease - mortality</topic><topic>Graft vs Host Disease - prevention & control</topic><topic>Health aspects</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - mortality</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Leukemia, Myeloid, Acute - therapy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Mud</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>original-article</topic><topic>Prognosis</topic><topic>Remission</topic><topic>Risk factors</topic><topic>Siblings</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Transplantation</topic><topic>Transplantation Conditioning</topic><topic>Transplantation, Homologous</topic><topic>Transplants</topic><topic>Transplants & implants</topic><topic>United Kingdom</topic><topic>Unrelated Donors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Russell, N H</creatorcontrib><creatorcontrib>Kjeldsen, L</creatorcontrib><creatorcontrib>Craddock, C</creatorcontrib><creatorcontrib>Pagliuca, A</creatorcontrib><creatorcontrib>Yin, J A</creatorcontrib><creatorcontrib>Clark, R E</creatorcontrib><creatorcontrib>Howman, A</creatorcontrib><creatorcontrib>Hills, R K</creatorcontrib><creatorcontrib>Burnett, A K</creatorcontrib><creatorcontrib>UK NCRI Adult AML Working Party</creatorcontrib><creatorcontrib>Written on behalf of the UK NCRI Adult AML Working 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Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russell, N H</au><au>Kjeldsen, L</au><au>Craddock, C</au><au>Pagliuca, A</au><au>Yin, J A</au><au>Clark, R E</au><au>Howman, A</au><au>Hills, R K</au><au>Burnett, A K</au><aucorp>UK NCRI Adult AML Working Party</aucorp><aucorp>Written on behalf of the UK NCRI Adult AML Working Party</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>29</volume><issue>7</issue><spage>1478</spage><epage>1484</epage><pages>1478-1484</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35–44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50–0.85),
P
=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01–2.21),
P
=0.04) due to lower NRM (34 vs 14%,
P
=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57–0.97),
P
=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35–44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (
P
=0.3).</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25376374</pmid><doi>10.1038/leu.2014.319</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Leukemia, 2015-07, Vol.29 (7), p.1478-1484 |
| issn | 0887-6924 1476-5551 |
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| source | MEDLINE; Nature; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | 692/308/575 Acute myelocytic leukemia Acute myeloid leukemia Adult Allografts Analysis Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cancer Research Care and treatment Chemotherapy Combined Modality Therapy Conditioning Critical Care Medicine Cytogenetics Female Follow-Up Studies Graft vs Host Disease - mortality Graft vs Host Disease - prevention & control Health aspects Health risk assessment Health risks Hematology Hematopoietic Stem Cell Transplantation Humans Intensive Internal Medicine Leukemia Leukemia, Myeloid, Acute - mortality Leukemia, Myeloid, Acute - pathology Leukemia, Myeloid, Acute - therapy Male Medicine Medicine & Public Health Middle Aged Mortality Mud Neoplasm Staging Oncology original-article Prognosis Remission Risk factors Siblings Stem cell transplantation Stem cells Survival Survival Rate Transplantation Transplantation Conditioning Transplantation, Homologous Transplants Transplants & implants United Kingdom Unrelated Donors |
| title | A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia |
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